6-42960723-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001318857.2(CNPY3-GNMT):c.152-2039C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,461,390 control chromosomes in the GnomAD database, including 161,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 16635 hom., cov: 34)

Exomes 𝑓: 0.47 ( 144565 hom. )

Consequence

CNPY3-GNMT
NM_001318857.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.329

Publications

45 publications found

Variant links:

COSMIC-nc: COSV55102851

Genes affected

GNMT (HGNC:4415): (glycine N-methyltransferase) The protein encoded by this gene is an enzyme that catalyzes the conversion of S-adenosyl-L-methionine (along with glycine) to S-adenosyl-L-homocysteine and sarcosine. This protein is found in the cytoplasm and acts as a homotetramer. Defects in this gene are a cause of GNMT deficiency (hypermethioninemia). Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between the upstream CNPY3 (canopy FGF signaling regulator 3) gene and this gene and is represented with GeneID:107080644. [provided by RefSeq, Jan 2016]

GNMT links:

PEX6 (HGNC:8859): (peroxisomal biogenesis factor 6) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. This member is a predominantly cytoplasmic protein, which plays a direct role in peroxisomal protein import and is required for PTS1 (peroxisomal targeting signal 1, a C-terminal tripeptide of the sequence ser-lys-leu) receptor activity. Mutations in this gene cause peroxisome biogenesis disorders of complementation group 4 and complementation group 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PEX6 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 4A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health
peroxisome biogenesis disorder 4B
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Heimler syndrome 2
Inheritance: AR Classification: MODERATE Submitted by: G2P
autosomal recessive cerebellar ataxia-blindness-deafness syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX6 links:

CNPY3-GNMT (HGNC:):

CNPY3-GNMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 6-42960723-C-T is Benign according to our data. Variant chr6-42960723-C-T is described in ClinVar as Benign. ClinVar VariationId is 1283888.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318857.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
CNPY3-GNMT	NM_001318857.2	c.152-2039C>T	intron	N/A	NP_001305786.1
CNPY3-GNMT	NM_001318856.2	c.9-1489C>T	intron	N/A	NP_001305785.1
CNPY3-GNMT	NM_001318858.2	c.152-2039C>T	intron	N/A	NP_001305787.1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
GNMT	ENST00000858685.1	c.-45C>T	5_prime_UTR	Exon 1 of 6	ENSP00000528744.1
GNMT	ENST00000858684.1	c.-45C>T	5_prime_UTR	Exon 1 of 6	ENSP00000528743.1
PEX6	ENST00000970120.1	c.*1761G>A	3_prime_UTR	Exon 18 of 18	ENSP00000640179.1

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69996

AN:

152082

Hom.:

16624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.459

GnomAD2 exomes

AF:

0.391

AC:

34529

AN:

88392

AF XY:

0.402

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.279

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.421

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.465

AC:

608822

AN:

1309190

Hom.:

144565

Cov.:

AF XY:

0.466

AC XY:

296459

AN XY:

636678

show subpopulations

African (AFR)

AF:

0.518

AC:

14913

AN:

28804

American (AMR)

AF:

0.299

AC:

8786

AN:

29396

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

8720

AN:

20714

East Asian (EAS)

AF:

0.143

AC:

4857

AN:

33990

South Asian (SAS)

AF:

0.461

AC:

31293

AN:

67854

European-Finnish (FIN)

AF:

0.413

AC:

15092

AN:

36502

Middle Eastern (MID)

AF:

0.492

AC:

2154

AN:

4374

European-Non Finnish (NFE)

AF:

0.483

AC:

498517

AN:

1033036

Other (OTH)

AF:

0.449

AC:

24490

AN:

54520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

16394

32789

49183

65578

81972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15222

30444

45666

60888

76110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.460

AC:

70048

AN:

152200

Hom.:

16635

Cov.:

AF XY:

0.455

AC XY:

33823

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.514

AC:

21351

AN:

41528

American (AMR)

AF:

0.361

AC:

5529

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1452

AN:

3470

East Asian (EAS)

AF:

0.127

AC:

659

AN:

5172

South Asian (SAS)

AF:

0.432

AC:

2083

AN:

4824

European-Finnish (FIN)

AF:

0.431

AC:

4564

AN:

10594

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.482

AC:

32744

AN:

67994

Other (OTH)

AF:

0.457

AC:

966

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1957

3914

5870

7827

9784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

642

1284

1926

2568

3210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.460

Hom.:

8007

Bravo

AF:

0.455

Asia WGS

AF:

0.290

AC:

1009

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.8

(source)

DANN

Benign

0.75

PhyloP100

-0.33

PromoterAI

-0.034

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over